Subregional Density of Neurons, Neurofibrillary Tangles and Amyloid Plaques in the Hippocampus of Patients With Alzheimer’s Disease

Alzheimer's disease (AD) is a complex, neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain. Glial cells, particularly microglial cells, react to the presence of the amyloid plaques and neurofibrillary tangles producing an inflammatory response. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. This paper will discuss the published literature regarding the diverse roles of neuroinflammation in the modulation of AD pathologies. These data will then be related to the well-characterized macrophage phenotypes. The conclusion is that the glial cells of the brain are capable of a host of macrophage responses, termed M1, M2a, M2b, and M2c. The relationship between these states and AD pathologies remains relatively understudied, yet published data using various inflammatory stimuli provides some insight. It appears that an M1-type response lowers amyloid load but exacerbates neurofibrillary tangle pathology. In contrast, M2a is accompanied by elevated amyloid load and appears to ameliorate, somewhat, neurofibrillary pathology. Overall, it is clear that more focused, cause-effect studies need to be performed to better establish how each inflammatory state can modulate the pathologies of AD.

Download Full-text

Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.11.114 ◽

2018 ◽

Vol 495 (1) ◽

pp. 1034-1040 ◽

Cited By ~ 25

Author(s):

Hong-Yan Cai ◽

Jun-Ting Yang ◽

Zhao-Jun Wang ◽

Jun Zhang ◽

Wei Yang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Neurofibrillary Tangles ◽

Amyloid Plaques ◽

Model Of Alzheimer’S Disease ◽

Tau Mouse Model

Download Full-text

Regulation of Melatonin and Neurotransmission in Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22136841 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6841

Author(s):

Jaydeep Roy ◽

Ka Chun Tsui ◽

Jonah Ng ◽

Man-Lung Fung ◽

Lee Wei Lim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Neurodegenerative Disorder ◽

Cognitive Impairments ◽

Amyloid Plaques ◽

Anxiety And Depression ◽

Melatonin Treatment ◽

The Impact ◽

Monoaminergic Neurotransmitter

Alzheimer’s disease is a neurodegenerative disorder associated with age, and is characterized by pathological markers such as amyloid-beta plaques and neurofibrillary tangles. Symptoms of AD include cognitive impairments, anxiety and depression. It has also been shown that individuals with AD have impaired neurotransmission, which may result from the accumulation of amyloid plaques and neurofibrillary tangles. Preclinical studies showed that melatonin, a monoaminergic neurotransmitter released from the pineal gland, is able to ameliorate AD pathologies and restore cognitive impairments. Theoretically, inhibition of the pathological progression of AD by melatonin treatment should also restore the impaired neurotransmission. This review aims to explore the impact of AD on neurotransmission, and whether and how melatonin can enhance neurotransmission via improving AD pathology.

Download Full-text

Pathophysiology of Alzheimer’s disease

10.1093/med/9780199569854.003.0004 ◽

2011 ◽

Author(s):

Shelley J. Allen ◽

David Dawbarn

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Early Onset ◽

Amyloid Plaques ◽

Progressive Dementia ◽

Familial Form

• Alzheimer’s disease (AD) is a progressive dementia with loss of neurons and the presence of two main microscopic neuropathological hallmarks: extracellular amyloid plaques and intracellular neurofibrillary tangles• Early onset AD, the rare familial form, is the result of a mutation in one of three genes: ...

Download Full-text

Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.750921 ◽

2021 ◽

Vol 13 ◽

Author(s):

Chen Chen ◽

Yao Chen ◽

Zhong-Hao Zhang ◽

Shi-Zheng Jia ◽

Yu-Bin Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Membrane Potential ◽

Energy Metabolism ◽

Mitochondrial Dysfunction ◽

Mitochondrial Membrane Potential ◽

Neurofibrillary Tangles ◽

Mitochondrial Function ◽

Mitochondrial Membrane ◽

Amyloid Plaques

Alzheimer’s disease (AD), the most common neurodegenerative disease in elderly humans, is pathologically characterized by amyloid plaques and neurofibrillary tangles. Mitochondrial dysfunction that occurs in the early stages of AD, which includes dysfunction in mitochondrial generation and energy metabolism, is considered to be closely associated with AD pathology. Selenomethionine (Se-Met) has been reported to improve cognitive impairment and reduce amyloid plaques and neurofibrillary tangles in 3xTg-AD mice. Whether Se-Met can regulate mitochondrial dysfunction in an AD model during this process remains unknown.In this study, the N2a-APP695-Swedish (N2aSW) cell and 8-month-old 3xTg-AD mice were treated with Se-Met in vitro and in vivo. Our study showed that the numbers of mitochondria were increased after treatment with Se-Met. Se-Met treatment also significantly increased the levels of NRF1 and Mfn2, and decreased those of OPA1 and Drp1. In addition, the mitochondrial membrane potential was significantly increased, while the ROS levels and apoptosis rate were significantly decreased, in cells after treatment with Se-Met. The levels of ATP, complex IV, and Cyt c and the activity of complex V were all significantly increased. Furthermore, the expression level of SELENO O was increased after Se-Met treatment. Thus, Se-Met can maintain mitochondrial dynamic balance, promote mitochondrial fusion or division, restore mitochondrial membrane potential, promote mitochondrial energy metabolism, inhibit intracellular ROS generation, and reduce apoptosis. These effects are most likely mediated via upregulation of SELENO O. In summary, Se-Met improves mitochondrial function by upregulating mitochondrial selenoprotein in these AD models.

Download Full-text

A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer’s disease

Science Advances ◽

10.1126/sciadv.1600947 ◽

2016 ◽

Vol 2 (8) ◽

pp. e1600947 ◽

Cited By ~ 54

Author(s):

Rosie Freer ◽

Pietro Sormanni ◽

Giulia Vecchi ◽

Prajwal Ciryam ◽

Christopher M. Dobson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Expression Patterns ◽

Amyloid Plaques ◽

Transcriptional Analysis ◽

Protein Homeostasis ◽

Tissue Specific ◽

Expression Signature ◽

Quantitative Correlation

In Alzheimer’s disease, aggregates of Aβ and tau in amyloid plaques and neurofibrillary tangles spread progressively across brain tissues following a characteristic pattern, implying a tissue-specific vulnerability to the disease. We report a transcriptional analysis of healthy brains and identify an expression signature that predicts—at ages well before the typical onset—the tissue-specific progression of the disease. We obtain this result by finding a quantitative correlation between the histopathological staging of the disease and the expression patterns of the proteins that coaggregate in amyloid plaques and neurofibrillary tangles, together with those of the protein homeostasis components that regulate Aβ and tau. Because this expression signature is evident in healthy brains, our analysis provides an explanatory link between a tissue-specific environmental risk of protein aggregation and a corresponding vulnerability to Alzheimer’s disease.

Download Full-text